Canine NAPEPLD-associated models of human myelin disorders

Canine leukoencephalomyelopathy (LEMP) is a juvenile-onset neurodegenerative disorder of the CNS white matter currently described in Rottweiler and Leonberger dogs. Genome-wide association study (GWAS) allowed us to map LEMP in a Leonberger cohort to dog chromosome 18. Subsequent whole genome re-sequencing of a Leonberger case enabled the identification of a single private homozygous non-synonymous missense variant located in the highly conserved metallo-beta-lactamase domain of the N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD) gene, encoding an enzyme of the endocannabinoid system. We then sequenced this gene in LEMP-affected Rottweilers and identified a different frameshift variant, which is predicted to replace the C-terminal metallo-beta-lactamase domain of the wild type protein. Haplotype analysis of SNP array genotypes revealed that the frameshift variant was present in diverse haplotypes in Rottweilers, and also in Great Danes, indicating an old origin of this second NAPEPLD variant. The identification of different NAPEPLD variants in dog breeds affected by leukoencephalopathies with heterogeneous pathological features, implicates the NAPEPLD enzyme as important in myelin homeostasis, and suggests a novel candidate gene for myelination disorders in people

LET spectra measurements of charged particles in the P0006 experiment on LDEF

Measurements are under way of the charged particle radiation environment of the Long Duration Exposure Facility (LDEF) satellite using stacks of plastic nuclear track detectors (PNTD's) placed in different locations of the satellite. In the initial work the charge, energy, and linear energy transfer (LET) spectra of charged particles were measured with CR-39 double layer PNTD's located on the west side of the satellite (Experiment P0006). Primary and secondary stopping heavy ions were measured separately from the more energetic particles. Both trapped and galactic cosmic ray (GCR) particles are included, with the latter component being dominated by relativistic iron particles. The results from the P0006 experiment will be compared with similar measurements in other locations on LDEF with different orientation and shielding conditions. The remarkably detailed investigation of the charged particle radiation environment of the LDEF satellite will lead to a better understanding of the radiation environment of the Space Station Freedom. It will enable more accurate prediction of single event upsets (SEU's) in microelectronics and, especially, more accurate assessment of the risk - contributed by different components of the radiation field (GCR's, trapped protons, secondaries and heavy recoils, etc.) - to the health and safety of crew members

Corporal diagnostic work and diagnostic spaces: Clinicians' use of space and bodies during diagnosis

© 2015 The Authors. Sociology of Health & Illness © 2015 Foundation for the Sociology of Health & Illness/John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.An emerging body of literature in sociology has demonstrated that diagnosis is a useful focal point for understanding the social dimensions of health and illness. This article contributes to this work by drawing attention to the relationship between diagnostic spaces and the way in which clinicians use their own bodies during the diagnostic process. As a case study, we draw upon fieldwork conducted with a multidisciplinary clinical team providing deep brain stimulation (DBS) to treat children with a movement disorder called dystonia. Interviews were conducted with team members and diagnostic examinations were observed. We illustrate that clinicians use communicative body work and verbal communication to transform a material terrain into diagnostic space, and we illustrate how this diagnostic space configures forms of embodied 'sensing-and-acting' within. We argue that a 'diagnosis' can be conceptualised as emerging from an interaction in which space, the clinician-body, and the patient-body (or body-part) mutually configure one another. By conceptualising diagnosis in this way, this article draws attention to the corporal bases of diagnostic power and counters Cartesian-like accounts of clinical work in which the patient-body is objectified by a disembodied medical discourse.The Wellcome Trust (Wellcome Trust Biomedical Strategic Award 086034

Plasminogen activator‐1 overexpression decreases experimental postthrombotic vein wall fibrosis by a non‐vitronectin‐dependent mechanism

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108289/1/jth12644.pd

Epidemiology of Aortic Aneurysm Repair in the United States from 1993 to 2003

The epidemiology of abdominal aortic aneurysm (AAA) disease has been well described over the preceding 50 years. This disease primarily affects elderly males with smoking, hypertension, and a positive family history contributing to an increased risk of aneurysm formation. The aging population as well as increased screening in high-risk populations has led some to suggest that the incidence of AAAs is increasing. The National Inpatient Sample (1993 2003), a national representative database, was used in this study to determine trends in mortality following AAA repair in the United States. In addition, the impact of the introduction of less invasive endovascular AAA repair was assessed. Overall rates of treated unruptured and ruptured AAAs remained stable (unruptured 12 to 15 100,000; ruptured 1 to 3 100,000). In 2003, 42.7 of unruptured and 8.8 of ruptured AAAs were repaired through an endovascular approach. Inhospital mortality following unruptured AAA repair continues to decline for open repair (5.3 to 4.7 , P 0.007). Mortality after elective endovascular AAA repair also has statistically decreased (2.1 to 1.0 , P 0.024) and remains lower than open repair. Mortality rates for ruptured AAAs following repair remain high (open: 46.5 to 40.7 , P 0.01; endovascular: 40.0 to 35.3 , P 0.823). These data suggest that the numbers of patients undergoing elective AAA repair have remained relatively stable despite the introduction of less invasive technology. A shift in the treatment paradigm is occurring with a higher percentage of patients subjected to elective endovascular AAA repair compared to open repair. This shift, at least in the short term, appears justified as the mortality in patients undergoing elective endovascular AAA repair is significantly reduced compared to patients undergoing open AAA repair.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73855/1/annals.1383.030.pd

Nanosized superparamagnetic precipitates in cobalt-doped ZnO

The existence of semiconductors exhibiting long-range ferromagnetic ordering at room temperature still is controversial. One particularly important issue is the presence of secondary magnetic phases such as clusters, segregations, etc... These are often tedious to detect, leading to contradictory interpretations. We show that in our cobalt doped ZnO films grown homoepitaxially on single crystalline ZnO substrates the magnetism unambiguously stems from metallic cobalt nano-inclusions. The magnetic behavior was investigated by SQUID magnetometry, x-ray magnetic circular dichroism, and AC susceptibility measurements. The results were correlated to a detailed microstructural analysis based on high resolution x-ray diffraction, transmission electron microscopy, and electron-spectroscopic imaging. No evidence for carrier mediated ferromagnetic exchange between diluted cobalt moments was found. In contrast, the combined data provide clear evidence that the observed room temperature ferromagnetic-like behavior originates from nanometer sized superparamagnetic metallic cobalt precipitates.Comment: 20 pages, 6 figures; details about background subtraction added to section III. (XMCD

Diffusion of Alexa Fluor 488-Conjugated Dendrimers in Rat Aortic Tissue

In this study, the distribution of labeled dendrimers in native and aneurysmal rat aortic tissue was examined. Adult male rats underwent infrarenal aorta perfusion with generation 5 (G5) acetylated Alexa Fluor 488-conjugated dendrimers for varying lengths of time. In a second set of experiments, rats underwent aortic elastase perfusion followed by aortic dendrimer perfusion 7 days later. Aortic diameters were measured prior to and postelastase perfusion, and again on the day of harvest. Aortas were harvested 0, 12, or 24 h postperfusion, fixed, and mounted. Native aortas were harvested and viewed as negative controls. Aortic cross-sections were viewed and imaged using confocal microscopy. Dendrimers were quantified (counts high-powered field). Results were evaluated by repeated measures ANOVA and Student's t -test. We found that in native aortas, dendrimers penetrated the aortic wall in all groups. For all perfusion times, fewer dendrimers were present as time between dendrimer perfusion and aortic harvest increased. Longer perfusion times resulted in increased diffusion of dendrimers throughout the aortic wall. By 24 h, the majority of the dendrimers were through the wall. Dendrimers in aneurysmal aortas, on day 0 postdendrimer perfusion, diffused farther into the aortic wall than controls. In conclusion, this study documents labeled dendrimers delivered intra-arterially to native rat aortas in vivo , and the temporal diffusion of these molecules within the aortic wall. Increasing perfusion time and length of time prior to harvest resulted in continued dendrimer diffusion into the aortic wall. These preliminary data provide a novel mechanism whereby local inhibitory therapy may be delivered locally to aortic tissue.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72448/1/annals.1383.004.pd

Comment on "X-ray resonant scattering studies of orbital and charge ordering in Pr1-xCaxMnO3"

In a recent published paper [Phys. Rev. B 64, 195133 (2001)], Zimmermann et al. present a systematic x-ray scattering study of charge and orbital ordering phenomena in the Pr1-xCaxMnO3 series with x= 0.25, 0.4 and 0.5. They propose that for Ca concentrations x=0.4 and 0.5, the appearance of (0, k+1/2, 0) reflections are originated by the orbital ordering of the eg electrons in the a-b plane while the (0, 2k+1, 0) reflections are due to the charge ordering among the Mn3+ and Mn4+ ions. Moreover, for small Ca concentrations (x<0.3), the orbital ordering is only considered and it occurs at (0, k, 0) reflections. A rigorous analysis of all these resonance reflections will show the inadequacy of the charge-orbital model proposed to explain the experimental results. In addition, this charge-orbital model is highly inconsistent with the electronic balance. On the contrary, these reflections can be easily understood as arising from the anisotropy of charge distribution induced by the presence of local distortions, i.e. due to a structural phase transition.Comment: 10 pages, 2 figures.To be published Phys. Rev.